Administration of Neomycin Resistance Gene Marked EBV Specific Cytotoxic T Lymphocytes to Recipients of Mismatched-Related or Phenotypically Similar Unrelated Donor Marrow Grafts. St. Jude Children's Research Hospital, Memphis, Tennesse

Heslop, Principal Investigators: Helen E.; Brenner, Malcolm K.; Rooney, Cliona M.; Krance, Co-Investigators: Robert A.; Roberts, WM; Rochester, Richard; Smith, Colton; Turner, Victoria; Sixbey, John W.; Moen, Robert C.; Boyett, James M.

doi:10.1089/hum.1994.5.3-381

Cited by 83 publications

(32 citation statements)

References 17 publications

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“…As an extension of this strategy, researchers have now demonstrated that administration of EBV-specific CTLs cultivated in vitro from donor lymphocytes is effective against EBV-LPDs. [183][184][185][186] For patients who are not candidates for DLI or EBV-specific CTL therapy, recent small case series have reported promising responses with the use of the anti-CD20 monoclonal antibody rituximab. 187,188 Rituximab is relatively safe and may prove to be as effective as DLI in the treatment of EBV-LPD.…”

Section: Ebv-lpdsmentioning

confidence: 99%

The history and future of T-cell depletion as graft-versus-host disease prophylaxis for allogeneic hematopoietic stem cell transplantation

Soiffer

2001

Blood

388

293

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Section: Ebv-lpdsmentioning

confidence: 99%

The history and future of T-cell depletion as graft-versus-host disease prophylaxis for allogeneic hematopoietic stem cell transplantation

Soiffer

2001

Blood

388

293

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“…32,33 PBMCs (2 ϫ 10 6 ) were cocultured with 5 ϫ 10 4 gamma-irradiated (40 Gy) autologous LCLs per well in a 24-well plate. Starting on day 10, the responder cells were restimulated weekly with irradiated (40 Gy) LCLs at a responder-to-stimulator ratio of 4:1.…”

Section: Generation Of Ebv-transformed B Cell Linesmentioning

confidence: 99%

Adapting a transforming growth factor β–related tumor protection strategy to enhance antitumor immunity

Bollard

Rössig

Calonge

et al. 2002

Blood

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306

213

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Transforming growth factor ␤ (TGF-␤), a pleiotropic cytokine that regulates cell growth and differentiation, is secreted by many human tumors and markedly inhibits tumor-specific cellular immunity. Tumors can avoid the differentiating and apoptotic effects of TGF-␤ by expressing a nonfunctional TGF-␤ receptor. We have determined whether this immune evasion strategy can be manipulated to shield tumor-specific cytotoxic T lymphocytes (CTLs) from the inhibitory effects of tumor-derived TGF-␤. As our model we used Epstein-Barr virus (

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“…In terms of delay, the selection of EBV-specific T cells requires the generation of an autologous B lymphoblastoid cell line (BLCL) 3 for use as an EBV APC, followed by a coculture with autologous PBMC. Several weeks are required to obtain the BLCL and several additional weeks are required to enrich for EBV-specific T cells (10). In terms of safety, BLCL are obtained after infection of autologous PBMC with an EBV viral strain produced by the marmoset B95.8 cell line, which is cultured in the presence of FCS.…”

mentioning

confidence: 99%

Purification of Ag-Specific T Lymphocytes After Direct Peripheral Blood Mononuclear Cell Stimulation Followed by CD25 Selection. I. Application to CD4+ or CD8+ Cytomegalovirus Phosphoprotein pp65 Epitope Determination

Gallot

Vivien

Ibisch

et al. 2001

The Journal of Immunology

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The two main constraints that currently limit a broader usage of T cell therapy against viruses are the delay required to obtain specific T cells and the safety of the selection procedure. In the present work we developed a generally applicable strategy that eliminates the need for APC for timing reasons, and the need for infectious viral strains for safety concerns. As a model, we used the selection of T lymphocytes specific for the immunodominant CMV phosphoprotein pp65. PBMC from healthy seropositive donors were first depleted of IL-2R α-chain CD25+ cells and were then stimulated for 24–96 h with previously defined peptide Ags or with autologous PBMC infected with a canarypox viral vector encoding the total pp65 protein (ALVAC-pp65). Subsequent immunomagnetic purification of newly CD25-expressing cells allowed efficient recovery of T lymphocytes specific for the initial stimuli, i.e., for the already known immunodominant epitope corresponding to the peptides used as a model or for newly defined epitopes corresponding to peptides encoded by the transfected pp65 protein. Importantly, we demonstrated that direct PBMC stimulation allowed recovery not only of CD8+ memory T lymphocytes, but also of the CD4+ memory T cells, which are known to be crucial to ensure persistence of adoptively transferred immune memory. Finally, our analysis of pp65-specific T cells led to the identification of several new helper and cytotoxic epitopes. This work thus demonstrates the feasibility of isolating memory T lymphocytes specific for a clinically relevant protein without the need to prepare APC, to use infectious viral strains, or to identify immunodominant epitopes.

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Administration of Neomycin Resistance Gene Marked EBV Specific Cytotoxic T Lymphocytes to Recipients of Mismatched-Related or Phenotypically Similar Unrelated Donor Marrow Grafts. St. Jude Children's Research Hospital, Memphis, Tennesse

Cited by 83 publications

References 17 publications

The history and future of T-cell depletion as graft-versus-host disease prophylaxis for allogeneic hematopoietic stem cell transplantation

The history and future of T-cell depletion as graft-versus-host disease prophylaxis for allogeneic hematopoietic stem cell transplantation

Adapting a transforming growth factor β–related tumor protection strategy to enhance antitumor immunity

Purification of Ag-Specific T Lymphocytes After Direct Peripheral Blood Mononuclear Cell Stimulation Followed by CD25 Selection. I. Application to CD4+ or CD8+ Cytomegalovirus Phosphoprotein pp65 Epitope Determination

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